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Diagnosis of uveitis is often challenging and developing an erudite differential diagnosis is a key to success.
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Classification of the uveitis is the first step and is guided by a serious of questions that can be answered from both the medical history and clinical examination.
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Classification of the uveitis and development of a list of potential diagnoses will help determine appropriate diagnostic testing, guide therapy, and help determine prognosis.
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Associated symptoms and signs are important sources of information and require a systemic review of symptoms and a detailed physical examination. Examination of the skin can be extremely rewarding in diagnosing uveitis. Referral to an internist, primary care physician, rheumatologist or other specialist is often required in the work-up of uveitis.
The correct diagnosis of uveitis is often challenging, not only for the general ophthalmologist but also for the uveitis specialist. Patients present with a plethora of ocular findings as well as associated systemic symptoms and signs. Ocular inflammation may be the initial presentation of an underlying systemic disease that, if undiagnosed and untreated, may lead to significant morbidity and even death. For example, we have seen a number of patients with intraocular lymphoma whose conditions were misdiagnosed and inappropriately treated as idiopathic uveitis. Even in patients with uveitis without an underlying systemic disease, misdiagnosis can lead to inappropriate therapy. A patient with fungal endophthalmitis who is thought to have sarcoidosis may be treated with corticosteroids, leading to an exacerbation of the infection, when appropriate antifungal therapy could be curative. In this chapter we review our diagnostic approach to patients with uveitis and present two cases to illustrate our approach.
Diagnosis is based largely on recognition of patterns that include findings from the medical history, clinical examination, and ordered tests, including laboratory tests and medical imaging. Medical experts are much better at recognizing the patterns consistent with medical diagnoses than are novices. Recent studies of memory suggest that this pattern recognition can be learned and takes practice. It should not be surprising, therefore, that doctors with many years of clinical practice are often better diagnosticians than less experienced care providers.
Much of what we know about memory and pattern recognition comes from the study of chess. In the 1960s De Groot , performed an intriguing study comparing the ability to recall chess patterns between players of varying abilities. A chessboard position, taken from a master game unknown to the subjects, was presented to participants for a short period varying from 2 to 15 seconds. Participants then had to reconstruct the board based on memory. The findings were dramatic. Grandmasters remembered board positions accurately, recalling an average of 93% of the pieces correctly after seeing the chess layout for only 2–5 seconds. The least experienced players only recalled about 50% of the pieces correctly. De Groot hypothesized that chess masters encode the positions of the pieces not as individuals but as groups. The data also suggest that the ability to recognize these patterns improves with experience, and can be learned with appropriate teaching and lots of practice.
The goal of this chapter is to provide the framework for clinicians to start collecting the information needed to form the disease patterns that help diagnose our patients. Knowing what questions to ask, what findings to look for, and what tests to order are all critical in seeing clear patterns from background noise. Every patient we see should help us fine tune our pattern recognition skills and allow us to better diagnose disease. First you need to collect the pieces of the puzzle that help us create the disease pattern. Second, you need to start putting the pieces together in ways that form several disease patterns. This is known as forming a differential diagnosis: identifying pieces of a puzzle that, when assembled, can form a handful of disease pictures. Finally, a specific diagnosis is made, often by ordering a key test that rules out all but one disease pattern. Recognizing potential disease patterns and forming a good differential diagnosis is the key to success.
Forming a differential diagnosis
The first step in developing a differential diagnosis for patients with inflammatory eye disease is to classify the uveitis in as detailed a fashion as possible. This can be achieved by systematically asking the eight questions listed in Box 4-1 . You can then generate a list of possible diagnoses by combining the data obtained from the answers. Some of the information is obtained from the history, such as the age and demographics of the patient and associated systemic symptoms. Other data, such as the type and anatomic location of the inflammation, are obtained from the ocular examination. Again, the need for information about systemic and neurologic signs necessitates a careful physical and neurologic examination of the patient by the ophthalmologist or by a consulting internist, internal medicine subspecialist, neurologist, or general medical practitioner.
- 1.
Is the disease acute or chronic?
- 2.
Is the inflammation granulomatous or nongranulomatous?
- 3.
Is the disease unilateral or bilateral?
- 4.
Where is the inflammation located in the eye?
- 5.
What are the demographics of the patient?
- 6.
What associated symptoms does the patient have?
- 7.
What associated signs are present on physical examination?
- 8.
What is the time course of the disease and response to previous therapy?
Once the uveitis has been classified, a preliminary differential diagnosis should be generated. The answers to each of the questions in Box 4-1 will generate a list of possible diagnoses. The diagnoses that appear most frequently on these lists are then the most likely cause of the disorder. Ancillary examinations, including laboratory tests or specialized examinations such as radiography, electrophysiology, or a surgical procedure such as a diagnostic vitrectomy, can then be obtained to discern among the most likely diagnoses. In the next chapter on diagnostic testing, we show that the ‘shotgun approach’ of ordering every diagnostic test available will mislead the clinician into making the wrong diagnosis.
Classifying uveitis
1.
Is the disease acute or chronic?
Acute occurrences of uveitis usually have a sudden onset and last up to 6 weeks. The most common causes are listed in Box 4-2 . Most occurrences of anterior uveitis, such as HLA-B27-associated iritis and idiopathic anterior uveitis, fall into this category. Other diseases that typically cause acute uveitis include Vogt–Koyanagi–Harada syndrome, postoperative bacterial infection, toxoplasmosis, many of the ‘white-dot syndromes,’ such as acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and multiple evanescent white-dot syndrome (MEWDS), and traumatic iritis. Although many diseases can cause acute uveitis, these are the conditions to consider first in the differential diagnosis. Chronic forms of uveitis have an insidious onset and typically last longer than 6 weeks. Other groups have defined a limited duration of uveitis as lasting 3 months or less, and persistent disease as lasting longer than 3 months. Again, although many diseases can cause a uveitis that persists longer than 6 weeks, the uveitides that are characteristically chronic are listed in Box 4-2 . Knowing whether the uveitis is acute or chronic is never sufficient to make a diagnosis, but it may aid in the diagnostic process.
ACUTE UVEITIS
Most cases of anterior uveitis: idiopathic, ankylosing spondylitis, Reiter’s syndrome, Fuchs’ heterochromic iridocyclitis
Vogt–Koyanagi–Harada syndrome
Toxoplasmosis
White-dot syndromes: acute posterior multifocal placoid pigment epitheliopathy and multiple evanescent white-dot syndrome
Acute retinal necrosis
Postsurgical bacterial infection
Trauma
CHRONIC UVEITIS
Juvenile rheumatoid arthritis
Birdshot choroidopathy
Serpiginous choroidopathy
Tuberculous uveitis
Postoperative uveitis ( Propionibacterium acnes , fungal)
Intraocular lymphoma
Sympathetic ophthalmia
Multifocal choroiditis
Sarcoidosis
Intermediate uveitis/pars planitis
2.
Is the inflammation granulomatous or nongranulomatous?
The ocular examination offers a unique opportunity to determine the type of infiltrating inflammatory cells involved in the disease process without taking a biopsy sample for histologic analysis. In anterior uveitis, inflammatory cells attach to the corneal endothelium in conglomerates called keratic precipitates (KPs). The appearance of KPs has been used to classify the inflammatory process as granulomatous or nongranulomatous. The more common nongranulomatous type of KP is characterized by fine white collections of lymphocytes, plasma cells, and pigment. These precipitates can form in any disease and cause an anterior uveitis; the finding of nongranulomatous KPs does not help tremendously in the formulation of a differential diagnosis other than to alert the clinician that anterior inflammatory disease has occurred in the eye. Granulomatous KPs are large, greasy-appearing collections of lymphocytes, plasma cells, and giant cells (see Fig. 4-2 ). The finding of granulomatous KPs, also called ‘mutton-fat’ KPs, on slit-lamp examination can be a useful diagnostic clue. Patients with granulomatous KPs usually have a history of a chronic disease with an insidious onset, and frequently have posterior segment disease in addition to their anterior segment inflammation. Other ocular findings suggestive of granulomatous inflammation are iris nodules and choroidal granulomas. Importantly, the finding of granulomatous inflammation in the eye suggests a unique set of diagnostic possibilities that are listed in Box 4-3 .
Sarcoidosis
Sympathetic ophthalmia
Uveitis associated with multiple sclerosis
Lens-induced uveitis
Intraocular foreign body
Vogt–Koyanagi–Harada syndrome
Syphilis
Tuberculosis
Other infectious agents
3.
Is the disease unilateral or bilateral?
Although one eye may be affected first, uveitis resulting from most causes involves both eyes within the first several months. Therefore, the history that the disease is both chronic and unilateral can help in diagnosing the condition. Diseases that frequently involve a single eye, even after months or years of the disorder, are listed in Box 4-4 . Parasitic disease typically involves one eye, although some of the diseases, such as toxoplasmosis, occur bilaterally. Uveitis after ocular surgery or the presence of an intraocular foreign body is almost exclusively unilateral. The one disease that most ophthalmologists think of as a bilateral disease but which we see involving a single eye in a number of patients is sarcoidosis. Similarly, we have seen a number of patients with Behçet’s disease that involved a single eye, especially those of Asian descent.
Sarcoidosis
Postsurgical uveitis
Intraocular foreign body
Parasitic disease
Acute retinal necrosis
Behçet’s disease
4.
Where is the inflammation located in the eye?
It is important to determine the anatomic position of the inflammation within the eye. Table 4-1 delineates three similar methods for the anatomic classification of intraocular inflammatory disease. We based our anatomic classification on the scheme proposed by the International Uveitis Study Group. This was modified by the SUN Working Group by dividing the anatomic nomenclature into anterior, intermediate, posterior, and panuveitis and functions to both simplify and standardize the way the disease is described. In addition to classifying uveitis as anterior, intermediate, or posterior uveitis or panuveitis, we note whether there is a predominant involvement of the cornea (keratouveitis), sclera (sclerouveitis), or retinal vasculature (retinal vasculitis) because these findings point to specific causes.
| IUSG * | Tessler † | SUN Working Group |
|---|---|---|
| – | Sclerouveitis | |
| – | Keratouveitis | |
| Anterior uveitis | Anterior uveitis | Anterior uveitis |
| Iritis | Iritis | Iritis |
| Anterior cyclitis | Iridocyclitis | Iridocyclitis |
| Iridocyclitis | Anterior cyclitis | |
| Intermediate uveitis (formerly known as pars planitis) | Intermediate uveitis | Intermediate uveitis |
| Posterior cyclitis | Cyclitis | Pars planitis |
| Hyalitis | Vitritis | Posterior cyclitis |
| Basal retinochoroiditis | Pars planitis | Hyalitis |
| Posterior uveitis | Posterior uveitis | Posterior uveitis |
| Focal, multifocal, or diffuse choroiditis | Choroiditis | Focal, multifocal or diffuse choroiditis |
| Chorioretinitis or retinochoroiditis | Retinitis | Retinitis, chorioretinitis, or retinochoroiditis |
| Neuroretinitis | – | Neuroretinitis |
| Panuveitis | – | Panuveitis |
* From Bloch-Michel E, Nussenblatt RB. International Uveitis Study Group recommendations for the evaluation of intraocular inflammatory disease. Am J Ophthalmol 1987; 103: 234–5.
† From Tessler HH. Classification and symptoms and signs of uveitis. In: Duane TD, Jaeger EA, eds. Clinical ophthalmology, vol 4. Philadelphia: JB Lippincott, 1987; 1–10.
Anterior uveitis describes a disease limited predominantly to the anterior segment of the eye. Other terms used in the literature for anterior uveitis are iritis, iridocyclitis, and anterior cyclitis. The inflammation is characterized by conjunctival hyperemia, anterior chamber cell and flare, KPs, and iris abnormalities, including posterior synechiae and peripheral anterior synechiae. A mild cellular inflammatory response in the anterior vitreous is often seen. The common causes of anterior uveitis are listed in Box 4-5 .
Idiopathic
Ankylosing spondylitis
Reiter’s syndrome
Inflammatory bowel disease
Psoriatic arthritis
Behçet’s disease
HLA-B27-associated disease
Juvenile rheumatoid arthritis
Fuchs’ heterochromic iridocyclitis
Sarcoidosis
Syphilis
Glaucomatocyclitic crisis
Masquerade syndromes
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